Variant 1-204619092-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_201630.2(LRRN2):c.901A>G(p.Ile301Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000056 in 1,608,290 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

LRRN2
NM_201630.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.49

Variant links:

Genes affected

LRRN2 (HGNC:16914): (leucine rich repeat neuronal 2) The protein encoded by this gene belongs to the leucine-rich repeat superfamily. This gene was found to be amplified and overexpressed in malignant gliomas. The encoded protein has homology with other proteins that function as cell-adhesion molecules or as signal transduction receptors and is a candidate for the target gene in the 1q32.1 amplicon in malignant gliomas. Two alternatively spliced transcript variants encoding the same protein have been described for this gene. [provided by RefSeq, Jul 2008]

LRRN2 links:

LOC105371692 (HGNC:):

LOC105371692 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29754376).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRN2	NM_201630.2 link	c.901A>G	p.Ile301Val	missense_variant	2/2	ENST00000367177.4	NP_963924.1	O75325A0A024R993

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LRRN2	ENST00000367177.4 link	c.901A>G	p.Ile301Val	missense_variant	2/2	1	NM_201630.2	ENSP00000356145.3	O75325
LRRN2	ENST00000367176.7 link	c.901A>G	p.Ile301Val	missense_variant	3/3	1		ENSP00000356144.3	O75325
LRRN2	ENST00000367175.1 link	c.901A>G	p.Ile301Val	missense_variant	1/1	6		ENSP00000356143.1	O75325

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1456084

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723536

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 01, 2022

The c.901A>G (p.I301V) alteration is located in exon 3 (coding exon 1) of the LRRN2 gene. This alteration results from a A to G substitution at nucleotide position 901, causing the isoleucine (I) at amino acid position 301 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.015

T;T;T

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.88

.;.;D

M_CAP

Benign

0.0053

MetaRNN

Benign

0.30

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.67

N;N;N

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.23

N;N;N

REVEL

Benign

0.18

Sift

Benign

0.51

T;T;T

Sift4G

Benign

0.31

T;T;T

Polyphen

1.0

D;D;D

Vest4

0.21

MutPred

0.51

Loss of catalytic residue at L306 (P = 0.0541);Loss of catalytic residue at L306 (P = 0.0541);Loss of catalytic residue at L306 (P = 0.0541);

MVP

0.51

MPC

0.54

ClinPred

0.43

GERP RS

5.7

Varity_R

0.046

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over